Magnetic resonance and fluorescence imaging of doxorubicin-loaded nanoparticles using a novel in vivo model

Erten, Ahmet; Wrasidlo, Wolf; Scadeng, Miriam; Esener, Sadik; Hoffman, Robert M.; Bouvet, Michael; Makale, Milan

doi:10.1016/j.nano.2010.06.005

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Volume 6, Issue 6 , Pages 797-807, December 2010

Magnetic resonance and fluorescence imaging of doxorubicin-loaded nanoparticles using a novel in vivo model

Ahmet Erten, MSEE
- Department of Nanoengineering, University of California San Diego, San Diego, California, USA
Wolf Wrasidlo, PhD
- University of California San Diego Moores Cancer Center, San Diego, California, USA
Miriam Scadeng, MD
- Department of Radiology, University of California San Diego, San Diego, California, USA
Sadik Esener, PhD
- Department of Nanoengineering, University of California San Diego, San Diego, California, USA
Robert M. Hoffman, PhD
- Department of Surgery, University of California San Diego, San Diego, California, USA
- AntiCancer Inc., San Diego, California, USA
Michael Bouvet, MD
- University of California San Diego Moores Cancer Center, San Diego, California, USA
- Department of Surgery, University of California San Diego, San Diego, California, USA
Milan Makale, PhD, MSEE
- University of California San Diego Moores Cancer Center, San Diego, California, USA
- Corresponding author:

Received 8 March 2010; accepted 14 June 2010. published online 05 July 2010.

Abstract

We report here the in vivo combined-modality imaging of multifunctional drug delivery nanoparticles. These dextran core–based stealth liposomal nanoparticles (nanosomes) contained doxorubicin, iron oxide for magnetic resonance imaging (MRI) contrast, and BODIPY for fluorescence. The particles were long-lived in vivo because of surface decoration with polyethylene glycol and the incorporation of acetylated lipids that were ultraviolet cross-linked for physical stability. We developed a rodent dorsal skinfold window chamber that facilitated both MRI and non-invasive optical imaging of nanoparticle accumulation in the same tumors. Chamber tumors were genetically labeled with DsRed-2, which enabled co-localization of the MR images, the red fluorescence of the tumor, and the blue fluorescence of the nanoparticles. The nanoparticle design and MR imaging developed with the window chamber were then extended to orthotopic pancreatic tumors expressing DsRed-2. The tumors were MR-imaged using iron oxide–dextran liposomes and by fluorescence to demonstrate the deep imaging capability of these nanoparticles.

From the Clinical Editor

In vivo combined-modality imaging of multifunctional drug delivery nanoparticles is discussed in this proof of principle paper.

Graphical Abstract

The figure depicts a multi-modality imaging-therapeutic nanoparticle containing iron oxide for MRI contrast, dextran hydrogel for drug loading, a lipid bilayer, PEGylated for evading the immune system and BODIPY for optical detection.